Thyroid hormone binding to plasma lipoproteins was studied in patients with hypothyroidism of brief duration and compared to normal subjects. Although hypothyroidism results in an increase in low density lipoproteins (LDL and VLDL), thyroid hormone binding to these proteins was decreased while it increased in the high density lipoprotein fraction (HDL). Both thyroxine (T4) and triiodothyronine (T3) are normally bound to relatively small size subfractions of HDL which are not identical. In hypothyroidism, the HDL subfraction that binds T4 increased in size, while that binding T3 decreased in size. The physiological consequence of this altered thyroid hormone transport are at present unknown.